Sodium hydride → 4-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine

HRID 1501488Notes

Reaction equation

HRID 1501488 reaction equation
CS(O[CH:6]1[CH2:15][CH2:14][C:9]2([O:13][CH2:12][CH2:11][O:10]2)[CH2:8][CH2:7]1)(=O)=O.[NH:16]1[CH:20]=[C:19]([C:21]2[C:22]3[CH:29]=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:23]=3[N:24]=[CH:25][N:26]=2)[CH:18]=[N:17]1.[H-].[Na+]>CN(C=O)C>[O:13]1[C:9]2([CH2:14][CH2:15][CH:6]([N:16]3[CH:20]=[C:19]([C:21]4[C:22]5[CH:29]=[CH:28][N:27]([CH2:30][O:31][CH2:32][CH2:33][Si:34]([CH3:37])([CH3:36])[CH3:35])[C:23]=5[N:24]=[CH:25][N:26]=4)[CH:18]=[N:17]3)[CH2:7][CH2:8]2)[O:10][CH2:11][CH2:12]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 149667411,4-Dioxaspiro(4.5)decan-8-yl methanesulfonateHCID 426313464-(1H-Pyrazol-4-yl)-7-(2-(trimethylsilyl)ethoxy)methyl-7 H-pyrrolo(2,3-d)-pyrimidine

Product 1

HCID 574779744-[1-(1,4-dioxaspiro[4.5]dec-8-yl)-1H-pyrazol-4-yl]-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 1,4-dioxaspiro[4.5]dec-8-yl methanesulfonate (0.50 g, 0.0015 mol) with 4-(1H-pyrazol-4-yl)-7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidine (0.36 g, 0.0011 mol) and sodium hydride (0.082 g, 0.0020 mol) was cooled at −78° C. and DMF (2.0 mL) was added. The reaction was allowed to warm to 25° C. and was then stirred for 20 minutes and was then heated to 55° C. for 24 hours. The reaction was then extracted with ethyl acetate. The organic extracts were washed with water and saturated NaCl, then dried (MgSO4) and concentrated in vacuo. The concentrate was chromatographed on silica gel using 1:1 EtOAc/hexanes to give the product. LC/MS (M+H)+: 456, 1H NMR (CDCl3): 8.89 (s, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 7.44 (d, 1H), 6.87 (d, 1H), 5.73 (s, 2H), 4.38 (m, 1H), 4.06 (s, 4H), 3.60 (m, 2H), 2.22-2.31 (m, 4H), 2.00 (m, 2H), 1.86 (m, 2H), 0.98 (m, 2H), 0.00 (s, 9H)

Workup

  1. temperatureto warm to 25° C.
  2. temperaturewas then heated to 55° C. for 24 hours
  3. extractionThe reaction was then extracted with ethyl acetate
  4. washThe organic extracts were washed with water and saturated NaCl
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe concentrate was chromatographed on silica gel using 1:1 EtOAc/hexanes
  8. customto give the product

Sources & evidence

ORD record
ord-21a9c1e5096b48489147bb467cad6ace
Source dataset
uspto-grants-2015_12
Patent number
US09206187B2

Reaction notes

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